Cardioprotection with Captopril added to Bretschneider-Solution: An in vitro rabbit heart study

While increased left ventricular mass (LVM) is strongly associated with incident heart failure (HF), events during transition from increased LVM to HF remain unclear. Extracellular non-coding RNAs (ex-RNAs) have been implicated in cardiac hypertrophy, though whether these ex-RNAs reflect important pathways in HF in humans is underexplored. In >2,000 individuals with concomitant M-mode echocardiography and ex-RNA measurements in the Framingham Heart Study, we found that lower circulating concentrations of three ex-RNAs—miR-20a-5p, miR-106b-5p, miR-17-5p—were associated with (1) greater LVM (+ one other pre-clinical phenotype, e.g., left atrial dimension or LVEDV) and (2) greater incident HF risk over a median follow-up 7.7 years ( Fig. A ). These 3 miRNAs were members of a tight cluster, regulating 883 mRNAs in common, associated with “hypertension” (OMIM) and biological process relevant to HF, including TGF-β signaling. We observed an increase in myocardial expression of these miRNAs during different phases of hypertrophy/HF development ( Fig. C, D ). Using gain and loss of function in vitro , our preliminary results suggest up-regulation of cardiomyocyte miR-106b expression abrogates expression of pathologic hypertrophy markers (ANP and BNP) during phenylephrine treatment, consistent with in silico results suggesting broad connections between miR-106b targets and natriuretic peptide signaling ( Fig. B, E-F ). These results provide translational evidence that circulating miRNAs associated with hypertrophy in patients may be protective in the transition from hypertrophy to HF at the molecular level.

Download Full-text

Neurofilament proteins are co-expressed with desmin in heart conduction system myocytes

Journal of Cell Science ◽

10.1242/jcs.97.1.11 ◽

1990 ◽

Vol 97 (1) ◽

pp. 11-21

Author(s):

M. Vitadello ◽

M. Matteoli ◽

L. Gorza

Keyword(s):

Subcellular Distribution ◽

Ultrastructural Level ◽

Rabbit Heart ◽

Cardiac Cells ◽

Structural Components ◽

Minor Population ◽

Neuronal Proteins ◽

Tissue Homogenates ◽

A Minor

We have recently shown that specialized myocytes of the rabbit heart express a cytoskeletal protein similar to the M subunit of neurofilaments (NF). Since this result was obtained using a single anti-NF-M monoclonal antibody, we tested on conduction myocytes a panel of five anti-NF antibodies, specific for each of the three NF subunits and for phosphorylated and non-phosphorylated epitopes. Two antibodies, one specific for the L subunit and one for phosphorylated M subunit of NF, reacted with specialized myocytes in immunohistochemistry. In immunoblots on conduction tissue homogenates the two antibodies recognized two polypeptides with electrophoretic mobility and solubility properties identical to those of NF-L and NF-M in the sciatic nerve. The subcellular distribution of NF immunoreactivity in specialized myocytes was very similar to desmin localization; namely, it was distributed on large filamentous bundles and on fine filaments localized transversely at the level of the Z line. At the ultrastructural level, immunoreactive filaments were localized in the intermyofibrillar space and connected myofibrils with mitochondria. Co-expression of NF proteins and desmin was also observed in vitro in a minor population of cardiac myocytes cultured from embryonic rabbit heart. In most cases NF immunoreactivity co-localized with desmin, especially where filaments were well organized, but in some cells anti-NF and anti-desmin antibodies labelled different filamentous structures. These results indicate that NF proteins are structural components of the cytoskeleton of specialized myocytes and show a subcellular distribution very similar to desmin. Such a composition of intermediate filaments indicates that in these cardiac cells muscle differentiation is compatible with the expression of neuronal proteins.

Download Full-text

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00209.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. H565-H573 ◽

Cited By ~ 20

Author(s):

Masahide Harada ◽

Yukiomi Tsuji ◽

Yuko S. Ishiguro ◽

Hiroki Takanari ◽

Yusuke Okuno ◽

...

Keyword(s):

Action Potential ◽

High Frequency ◽

Rabbit Heart ◽

Left Ventricular ◽

High Frequency Stimulation ◽

Electrophysiological Properties ◽

Rate Dependent ◽

Frequency Stimulation ◽

And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Download Full-text

Tissue specific peculiarities of vibration-induced hypoxia of the rabbit heart, liver and kidney

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf14146-62 ◽

2016 ◽

Vol 14 (1) ◽

pp. 46-62 ◽

Cited By ~ 1

Author(s):

Viktoriya V Vorobieva ◽

Petr D Shabanov

Keyword(s):

Succinic Acid ◽

Energy Production ◽

Pharmacological Action ◽

Rabbit Heart ◽

Tissue Type ◽

Metabolic States ◽

Before And After ◽

Liver And Kidney ◽

Endogenous Substrates

The purpose of the paper was experimental study of activity of energy production of the heart, liver and kidney after harmful action of general vibration with 8 and 44 Hz frequency. The functional state of native mitochondria in tissue homogenates was studied by polarographic method by means of closed oxygen device of halvanic type in thermostated cuvette of 1 ml volume in the salt medium of incubation. Metabolic states of mitochondria of the rabbit heart, liver and kidney were modeled in vitro in oxidation of endogenous substrates (before and after administration of inhibitors of different stages of breath chain) varying exogenous substrates (before and after administration of 2.4-DNP into the cell). In order to synchronize the changes in short time, the incomplete cycle of metabolic states “endogenous breath → rest → activity” was used. The velocity of mitochondrial oxidation of endogenous substrates was determined by tissue type, and was 16.3 ± 4.3, 5.2 ± 0.6 and 8.13 ± 1.4 ng-atom О min-1mg-1 protein for the heart, liver and kidney of intact animals respectively. In the heart, after high frequent vibration, the reduction of oxidation velocity of NAD-dependent substrates in rest and in active metabolic state of mitochondria was 43 % (р ≤ 0.05) and 30 % (р ≤ 0.01) respectively, while the velocity of oxidation for endogenous succinic acid increased by 77 % (р ≤ 0.05) to 21st session of vibration, then constantly decreasing to the end of vibration sessions. The same changes but in less degree were registerted in the liver and kidney. The systems of energy production of the heart and the studied parenchimatic organs were involved in reaction on vibration exposure and reacted typically by low energetic shift with hyperactivation of endogenous succinic acid system of oxidation and inhibition of NAD-depended part of the breath chain of mitochondria. Therefore, the study of bioenergetics mechanisms of hypoxia in different tissues allows to clear the molecular targets for pharmacological action by means of substrate antihypoxants.

Download Full-text

Mechanisms of Ventricular Arrhythmias Induced by Myocardial Contusion

Anesthesiology ◽

10.1097/00000542-200004000-00032 ◽

2000 ◽

Vol 92 (4) ◽

pp. 1132-1143 ◽

Cited By ~ 24

Author(s):

Emmanuelle Robert ◽

Jean E. de La Coussaye ◽

Antoine G. M. Aya ◽

Jean-Pierre Bertinchant ◽

Anne Polge ◽

...

Keyword(s):

Kinetic Energy ◽

Conduction Block ◽

Rabbit Heart ◽

Control Group ◽

Myocardial Contusion ◽

Refractory Periods ◽

Heart Study ◽

Resolution Mapping ◽

Ventricular Tachycardias ◽

Intact Heart

Background The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. Methods Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. Results The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. Conclusions Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.

Download Full-text

QT prolongation by non-cardiovascular CNS targeting drugs in the rabbit heart in vitro and in vivo

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(02)90805-9 ◽

2002 ◽

Vol 34 (6) ◽

pp. A20

Author(s):

László Dézsi ◽

Éva Makó ◽

Zsolt Komlódi ◽

Sándor Farkas

Keyword(s):

Rabbit Heart ◽

Qt Prolongation ◽

Cns Targeting

Download Full-text

The factor VII activating protease G511E (Marburg) variant and cardiovascular risk

Thrombosis and Haemostasis ◽

10.1160/th04-05-0275 ◽

2004 ◽

Vol 92 (11) ◽

pp. 986-992 ◽

Cited By ~ 42

Author(s):

George Miller ◽

Karen E.Webb ◽

Jackie Cooper ◽

Steve Humphries ◽

Helen Ireland

Keyword(s):

Interaction Analysis ◽

Interactive Effect ◽

Strong Relationship ◽

Factor Vii ◽

Prothrombotic State ◽

Heart Study ◽

Coagulant Activity ◽

Cardio Vascular ◽

A Prospective Study

SummaryA previous study had shown a strong relationship between a variant in factor VII activating protease (FSAP G511E) and advanced carotid atheroma. In-vitro, the variant has reduced fibrinolytic but normal pro-coagulant activity, which may constitute a prothrombotic state. The current study has addressed risk for coronary heart disease in a prospective study of cardio-vascular disorders (Northwick Park Heart Study II). An interactive effect upon risk was found between the 511E allele and elevated levels of cholesterol and triglyceride. Fibrinogen could substitute for triglyceride levels in this risk-interaction analysis. The findings support the proposal that the FSAP 511E allele exacerbates atherosclerosis or its clinical sequelae.

Download Full-text